A Strontium Ranelate Incorporated Enzyme-Crosslinked Gelatin Nanoparticle/Silk Fibroin Aerogel For Osteogenesis In OVX-Induced Osteoporosis

Background: Osteoporosis is a wide-range disease with negative impact on bone defects healing.Strontium ranelate(SR)has promising osteogenic potential for its dual function on stimulating osteoblasts and inhibiting osteoclasts activity.However,it has limitations for its dose-dependent effect and side effects on systemic application.Method: Here,a sequentially crosslinking strategy including enzyme-crosslinking through tyrosinase from mushroom and physical folding is acquired to create SR loaded gelatin nanoparticle/silk fibroin aerogel(abbreviated as S/G-Sr-MT)with drug release controlling capacity.Results: The results showed successful enzyme-crosslinking,excellent spatial structure and enhanced mechanical of S/G-Sr-MT.Evenly Sr2+ loading and stable release with markedly inhibited initial burst release was detected.Biomineralization investigation showed rapid deposition of hydroxyapatite on the surface of S/G-Sr-MT.In vitro,spreading morphology and higher osteogenic gene expression of MC3T3-E1 seeded on S/G-Sr-MT were observed compared to other groups after 7-day culturing.In vivo,S/G-Sr-MT showed obvious osteogenic capacity in calvaria defects of ovariectomized rats in which high Runx2 expression and inhibited TRAP activity were observed.Conclusion: Such results suggested the S/G-Sr-MT scaffold could stimulate osteogenic differentiation of osteoblasts while inhibit osteoclast behaviors in vivo.These findings highlight the potential osteogenic ability and clinical application of SR incorporated enzyme-crosslinked scaffold in ovariectomized(OVX)bone healing.